What are the primary causes and risk factors for stroke?

Causes of Stroke

Stroke results from two fundamental mechanisms: ischemic injury (85% of cases) caused by arterial occlusion, and hemorrhagic injury (15% of cases) caused by vessel rupture, with hypertension being the single most important modifiable risk factor for both types. 1, 2

Primary Stroke Mechanisms

Ischemic Stroke Causes (85% of all strokes)

• Large-vessel atherosclerosis accounts for 20% of ischemic strokes, affecting extracranial or intracranial segments of carotid or vertebrobasilar arteries through atherosclerotic plaque formation, rupture, and thromboembolism 1

• Small vessel disease (penetrating artery disease) causes 25% of ischemic strokes, producing lacunar or subcortical infarcts through arteriolosclerosis of small perforating vessels 1, 2

• Cardiogenic embolism accounts for 20% of ischemic strokes, predominantly from atrial fibrillation where thrombi form in the heart and embolize to cerebral vessels 1, 2

• Cryptogenic stroke represents 30% of ischemic strokes where the exact cause remains unknown despite thorough evaluation 1

Hemorrhagic Stroke Causes (15% of all strokes)

• Intracerebral hemorrhage (ICH) comprises 10-15% of all strokes, with hypertension being the primary cause of deep hemorrhages in basal ganglia and brainstem through arteriolosclerosis of deep perforating vessels 3, 2

• Cerebral amyloid angiopathy is the main cause of lobar hemorrhages, particularly in elderly patients 2

• Vascular malformations (arteriovenous malformations, cavernomas, aneurysms) account for approximately 20% of ICH, especially important in patients under 50 years 3

• Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes, with ruptured cerebral aneurysms being the leading cause 3, 1

• Anticoagulant use and bleeding disorders significantly increase ICH risk 3

Major Risk Factors

Nonmodifiable Risk Factors

• Age is the most powerful nonmodifiable risk factor, with stroke risk doubling for each decade after age 55, making an 85-year-old have approximately 8 times the stroke risk of a 55-year-old 4

• Race and ethnicity significantly impact risk: American Indian/Alaskan Native persons have the highest prevalence (6.7%), Black individuals have twice the prevalence of whites, and Hispanic/Latino men have higher prevalence (3.1%) compared to non-Hispanic white men (2.4%) 1

• Genetic factors contribute substantially, with monozygotic twins showing nearly 5-fold higher concordance rates compared to dizygotic twins 4, 5

Well-Documented Modifiable Risk Factors

• Hypertension is the major modifiable risk factor for both cerebral infarction and intracerebral hemorrhage, affecting at least 65 million Americans with a continuous, consistent, and independent relationship between blood pressure and stroke risk 4, 5

• Antihypertensive therapy reduces stroke risk by 35-44%, with blood pressure targets of <140/90 mmHg in the general population and lower targets (<140/90 mmHg) for patients with diabetes 4, 5

• Atrial fibrillation is a major cause of cardioembolic strokes, representing one of the most significant cardiac risk factors 4, 1

• Atherosclerotic vascular disease in other beds (coronary heart disease, cardiac failure, or symptomatic peripheral arterial disease) substantially increases stroke risk with relative risks of 1.73 for men and 1.55 for women 5, 4

• Diabetes mellitus is associated with 9.1% of recurrent strokes and substantially increases first-stroke risk through accelerated atherosclerosis and endothelial dysfunction 4

• Cigarette smoking is a major modifiable risk factor, with smoking cessation reducing stroke risk by approximately 38% 4

• Physical inactivity substantially increases stroke risk, with fewer than 20% of Americans engaging in regular physical activity 4

• Obesity increases stroke risk and accounts for up to 40% of all hypertension cases 4

• Alcohol abuse increases stroke risk, particularly for hemorrhagic stroke 3, 5

• Drug abuse (cocaine, heroin, methamphetamines) is associated with increased stroke risk through multiple mechanisms including sudden blood pressure surges, vasculitis, and vasculopathy 5

Less Well-Documented Risk Factors

• Hypercoagulable states including antiphospholipid antibodies have been associated with ischemic stroke in case-control studies, though their role in primary prevention remains unclear 5

• Sleep-disordered breathing (obstructive sleep apnea) is increasingly recognized as a stroke risk factor and should be assessed in patients with resistant hypertension 4

• Migraine with aura may be associated with increased stroke risk in certain populations 4

Critical Clinical Considerations

Modifiable risk factors account for approximately 90% of the population-attributable risk for stroke, meaning aggressive modification has the potential to prevent the vast majority of strokes 4

Common Pitfalls to Avoid

• Do not underestimate blood pressure control: Even modest reductions translate to substantial stroke risk reduction, yet only 34% of Americans with hypertension have controlled blood pressure (<140/90 mmHg) 5

• Do not overlook atrial fibrillation screening: This represents one of the most treatable causes of cardioembolic stroke, particularly in older patients 4

• Do not ignore the cumulative effect of multiple risk factors: Patients with several modifiable risk factors require aggressive, comprehensive intervention with potential for up to 80% reduction in recurrent stroke risk 4

• Do not neglect pregnancy-related stroke risk: Pregnant and postpartum individuals have approximately triple the stroke risk, with severe hypertension (≥160/110 mmHg) requiring immediate treatment to prevent fatal maternal ICH 5